This invention relates to the synthesis of secondary amines containing phosphonyl and carbonyl groups and, more particularly, to an improved process for producing N-phosphonomethylglycine or derivatives thereof by reductive alkylation.
N-phosphonomethylglycine, known in the agricultural chemical art as glyphosate, is a highly effective and commercially important phytotoxicant useful in controlling the growth of germinating seeds, emerging seedlings, maturing and established woody and herbaceous vegetation, and aquatic plants. Glyphosate and salts thereof are conveniently applied in an aqueous formulation as a post-emergent phytotoxicant or herbicide for the control of one or more monocotyledonous species and one or more dicotyledonous species. Moreover, such compounds are characterized by broad spectrum activity, i.e., they control the growth of a wide variety of plants, including but not limited to ferns, conifers, aquatic monocotyledons, and dicotyledons.
Hershman, U.S. Pat. No. 3,969,398, describes a process for preparing glyphosate in which iminodiacetic acid is reacted with formaldehyde and phosphorous acid to produce N-phosphonomethyliminodiacetic acid as an intermediate. This is then oxidized in the presence of a carbon catalyst to produce glyphosate.
Gaertner, Canadian Patent 1,039,739, describes a process for producing glyphosate by reacting aminomethylphosphonic acid and its esters with glyoxal or glyoxylic acid to form carbonylaldiminomethanephosphonates. Thereafter, the carbonylaldiminomethanephosphonates are subjected to catalytic hydrogenation to reduce the double bond and produce glyphosate acid or its esters. The ester groups are then hydrolyzed to produce N-phosphonomethylglycine. Both the condensation of aminomethylphosphonate with an aldehyde and catalytic hydrogenation of the resultant imine are carried out in organic solvents. For the condensation reaction the solvent is an aromatic hydrocarbon, such as benzene, toluene, or xylene, while catalytic hydrogenation is typically carried out in an alcohol.
Franz, U.S. Pat. No. 3,799,758, describes the preparation of glyphosate by reaction of ethyl glycinate, formaldehyde, and diethyl phosphite. Alternative processes described by Franz include phosphonomethylation of glycine with chloromethylphosphonic acid in the presence of sodium hydroxide and oxidation of N-phosphinomethylglycine with mercuric chloride.
Gaertner, U.S. Pat. No. 3,927,080, describes the production of glyphosate by acid hydrolysis and dealkylation of N-t-butyl-N-phosphonomethylglycine or its esters. Tertiary butyl amine is reacted with a bromoacetate ester to produce an ester of N-t-butyl-glycine, which is in turn reacted with formaldehyde and phosphorous acid to produce the N-t-butyl-N-phosphonomethylglycine precursor.
Ehrat, U.S. Pat. No. 4,237,065, describes a process in which N-phosphonomethylglycine is prepared starting from glycine, formaldehyde and a tertiary base in an alcoholic solution. After completion of the reaction, a dialkyl phosphite is added and the reaction product is hydrolyzed and then acidified to precipitate the product.
While Gaertner, as described in his aforesaid Canadian patent, achieved monoalkylation of aminomethylphosphonic acid by the sequential process of first condensing aminomethylphosphonic acid or its esters with glyoxylic acid and its esters to produce the aldimine and thereafter subjecting the aldimine to catalytic hydrogenation, there are other references which describe the in situ reduction of the condensation products of various amines and aldehydes. Such condensation and in situ reduction is generally referred to in the art as reductive alkylation. However, when the aldimino structure obtained by condensation of a primary amine with an aldehyde is reduced in situ, the resultant secondary amine can further react with the aldehyde to produce a hemiaminal or an aminal which is in turn reduced by hydrogenolysis, resulting in the formation of a tertiary amine. Thus, the result is typically substantial dialkylation rather than the substantially exclusive monoalkylation that is preferred in the preparation of an end product, such as glyphosate.
Ikutani, "Studies of the N-Oxides of N,N-Dialkyl Amino Acids. II. The Syntheses of N,N-Dialkylglycine and Corresponding N-Oxides", Bulletin of the Chemical Society of Japan, Volume 42, pp. 2330-2332, reports the reductive condensation of glycine with various aliphatic aldehydes. Only with relatively hindered aldehydes did Ikutani recover any monoalkylated product after reactions at 40.degree. C. to 50.degree. C. for periods of 3 to 9 hours. In the case of acetaldehyde, propionaldehyde, and N-butyraldehyde, at best a trace of monoalkyl product was recovered, while the dialkyl yields ranged from 41% to 83%.
Bowman, "N-Substituted Amino Acids. Part II. The Reductive Alkylation of Amino Acids", Journal of the Chemical Society (1950), p. 1346, reported that experiments on the alkylation of glycine by means of acetaldehyde, propionaldehyde, N-butanal, and N-heptanal, under conditions favorable to the formation of monoalkyl derivatives, failed to reveal any evidence of partial alkylation.
Moser, U.S. Pat. No. 4,369,142, describes a process for the preparation of N-phosphonomethylglycine in which aminomethylphosphonic acid is reacted in aqueous medium with glyoxal in the presence of sulfur dioxide.
In DE 2,725,669 there is disclosed a process for the preparation of secondary amines under hydrogenation conditions in the presence of a catalyst comprising nickel or cobalt and a quaternary ammonium compound. High yields are reported.
Mono-substituted amino acids, such as glycines and alanines, are prepared by a process disclosed in EPO 0079767 wherein a primary amino group and a ketone are reacted under reductive condensation conditions in the presence of a reductant and a hydrogenation catalyst under conditions of elevated temperature and superatmospheric conditions. Nobel metal catalysts are described and the preferred catalyst is palladium on carbon.
H. Yanagawa et al, "Novel Formation of .alpha.-Amino Acids and Their Derivatives from Oxo Acids and Ammonia in an Aqueous Medium", J. Biochem, 91, 2087-2090 (1982) discloses the reaction of glyoxylic acid with ammonia, methylamine, and ammonium sulfate to make glycine and/or its derivatives. On page 2088 in Table I, the synthesis of various amino acids is disclosed at pH 4 and pH 8 and at temperatures of 27.degree. C. and 105.degree. C. At the bottom of the left column bridging to the top of the right column on page 2088, it is disclosed that acidic pH and low temperatures were more favorable than alkaline pH and high temperatures for the formation of glycine.
J. Kihlberg, "Synthesis of Strombine. A New Method for Monocarboxymethylation of Primary Amines", Acta Chemica Scandinavica B 37, 911-916 (1983) discloses the reaction of two equivalents of glyoxylic acid with primary aliphatic and aromatic amines, which proceeds via the initial formation of an intermediate imine compound. In Table I, appearing on page 914, it is disclosed that various starting amines are reacted with 2 equivalents of glyoxylic acid at temperatures between about 25.degree. C. and 70.degree. C.
Although the teachings of the above references, alone or in combination, can be used to produce satisfactory yields of N-phosphonomethylglycine (glyphosate), each of such teachings suffer from one or more disadvantages. Now, there is provided a straightforward process for the production of glyphosate or its derivatives, without the necessity of isolating intermediate products, in high yields and with high selectivity, (i.e. the ratio of glyphosate produced to the theoretical amount based on the phosphonate starting material).